A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States

Lappalainen, Jaakko; Kranzler, Henry R.; Malison, Robert T.; Price, Lawrence H.; Dyck, Christopher van; Rosenheck, Robert A.; Cramer, Joyce A.; Southwick, Steven M.; Charney, Dennis S.; Krystal, John H.; Gelernter, Joel

doi:10.1001/archpsyc.59.9.825

Cited by 160 publications

(106 citation statements)

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“…Several of the genes that are central to drug response and neuroadaptation have already been tested as leading candidates in genetic studies in humans. So far, the brain-derived neurotrophic factor (BDNF) 115 , the 5-hydroxytryptamine (serotonin) receptor 1B (HTR1B) 24 , the γ-aminobutyric acid receptor A (GABA A ) receptor 38 , neuropeptide Y (NPY) 116 , and the dopamine D2 receptor (DRD2) 117 genes have been implicated in animal studies and evaluated in humans, with promising results. However, most of the strong candidate genes to emerge from animal neurobiological studies of addiction have yet to be evaluated for sequence variation and linkage to human addictive behaviour.…”

Section: Discussionmentioning

confidence: 99%

The genetics of addictions: uncovering the genes

2005

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Section: Discussionmentioning

confidence: 99%

The genetics of addictions: uncovering the genes

2005

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“…The attributable fraction, which is the proportion of cases in the study population that would not have occurred had the risk factor (risk allele) not been present, is a useful measure to quantify the impact of the allele on the development of PTSD. [25] The analysis revealed that 14% of the susceptibility to PTSD could be attributed to having the CC genotype of the 957C4T DRD2 polymorphism.…”

Section: Discussionmentioning

confidence: 99%

The DRD2 gene 957C>T polymorphism is associated with Posttraumatic Stress Disorder in war veterans

et al. 2009

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Background: Variations in genes related to the dopaminergic pathway have been implicated in neuropsychiatric disorders such as schizophrenia, substance misuse, Alzheimer's disease and Post Traumatic Stress Disorder (PTSD). A single nucleotide polymorphism (SNP) (957C4T) and a deletion polymorphism (-141delC) in the DRD2 gene and a SNP (Taq1A) in a gene directly downstream of DRD2 have all been implicated in dopamine functioning in the brain. Methods: To test the importance of these three polymorphisms in PTSD susceptibility, a genetic screen was performed in 127 war veterans diagnosed with PTSD and 228 control individuals without a history of PTSD. Results: No significant association was found between PTSD and the Taq1A or -141delC polymorphisms. However, a significant association was observed with PTSD and the 957C4T polymorphism. PTSD individuals were more likely to carry the C allele compared to the controls (P 5 0.021). Conclusions: Our findings suggest that the 957C4T polymorphism in the DRD2 gene is one of the genetic factors for susceptibility to PTSD. Depression Anxiety 26: 28-33, 2009.

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“…We believe that these data add meaningfully to the existing findings in the study of the molecular genetics of alcoholism. Many genes, such as certain alcohol dehydrogenases and aldehyde dehydrogenase, 27 neuropeptide Y, 28 and GABA-A receptor, 29 have already been implicated in genetic risk for alcoholism. To our knowledge, this is the second fine-mapping report focusing on the genetic background of alcoholism using a positional strategy.…”

Section: Discussionmentioning

confidence: 99%

Confirmation and fine mapping of the chromosome 1 alcohol dependence risk locus

Lappalainen

Petrakis

et al. 2004

Mol Psychiatry

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Two previous large genetic linkage studies in the US population have implicated an area in chromosome 1p to contain a susceptibility gene for alcohol dependence. The 1-LOD support interval of the linkage signal spans about 30 cM and contains 430 000 000 DNA base pairs (bp) and 700 predicted genes. In order to reduce the size of the candidate area and potentially identify novel candidate genes within this region, we fine-mapped this area using closely spaced short tandem repeat (STR) markers and the transmission disequilibrium test (TDT) in small nuclear families. The subjects were 87 European-American families including one or more alcohol-dependent offspring (93 children and 174 parents). The initial marker set consisted of 30 STR markers, spanning the Marshfield map interval between 101.48 and 130.73 cM. Using the TDTPHASE program, we identified three markers in the distal part of this region (125-126 cM), which showed evidence of transmission disequilibrium. On the basis of this result, an additional 12 STR markers were genotyped in this region; some of these markers provided additional evidence for linkage disequilibrium. The strongest evidence for transmission disequilibrium was obtained at the marker D1S406 (P¼0.005, 126.16 cM), with supporting evidence from three neighboring STR markers D1S424 (126.16 cM, P¼0.01), D1S2804 (126.16 cM, P¼0.04), and D1S2776 (126.16 cM, P¼0.02), which are all located within a o350 000 bp interval. These findings suggest that a gene (or genes) causing susceptibility to alcohol dependence resides near location 126.16 cM on chromosome 1. In addition, these results provide independent confirmation of the linkage finding regarding the identification of at least one gene in this region increasing the risk for alcohol dependence.

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A Functional Neuropeptide Y Leu7Pro Polymorphism Associated With Alcohol Dependence in a Large Population Sample From the United States

Abstract: These results suggest that the NPY Pro7 allele is a risk factor for alcohol dependence. This is only the second specific genetic mechanism ever identified that modulates risk for alcohol dependence.

Cited by 160 publications

References 36 publications

The genetics of addictions: uncovering the genes

The genetics of addictions: uncovering the genes

The DRD2 gene 957C>T polymorphism is associated with Posttraumatic Stress Disorder in war veterans

Confirmation and fine mapping of the chromosome 1 alcohol dependence risk locus

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